Citrate Versus Heparin Anticoagulation For CRRT:A Meta-analysis

Background: Continuous renal replacement therapy(CRRT) is commonly used for critically ill patients with acute kidney injury, severe metabolic acidosis/alkalosis disorders, refractory fluid overload, and certain drug intoxications. Clotting in the extracorporeal circuit shortens the filter and catheter lifespans, causes blood loss, and decreases solute clearing efficacy, consequently reduces the effectiveness of CRRT and increases the cost and workload of treatment. Several studies and meta-analyses have evaluated the efficacy of citrate versus heparin anticoagulation for CRRT, the results of these studies were controversial.Aim: To evluate the efficacy of citrate versus heparin anticoagulation for CRRT by performing a updated meta-analysis.Methods: We searched the Medline, Embase, and Cochrane databases from their inception to 6 April 2015. Eligible studies were identified using the following key terms: citrate, heparin, anticoagulation, CRRT, continuous renal replacement therapy, CVVH, continuous venovenous hemofiltration, CVVHD, continuous venovenous hemodialysis,CVVHDF, and continuous venovenous hemodiafiltration. Studies with the following characteristics were considered as the candidate for inclusion:(1) the interventions were citrate versus heparin anticoagulation for CRRT and(2) the included patients were randomly assigned to the treatment groups. The assessed outcomes included circuit loss(circuit termination for any reason), filter failure, catheter dysfunction, patient mortality, bleeding episodes, HIT, metabolic alkalosis disturbances, and hypocalcemia.Results: Eleven RCTs with 992 patients and 1998 circuits were included in our present meta-analysis. Heparin was regionally delivered in two trials and systemically delivered in nine trials. Citrate anticoagulation for CRRT significantly reduced the risk of circuit loss compared to regional(HR 0.52, 95 % CI 0.35–0.77, P = 0.001) and systemic(HR 0.76, 95 % CI 0.59–0.98, P = 0.04) heparin. Citrate anticoagulation also reduced the incidence of filter failure(RR 0.70, 95 % CI 0.50–0.98, P = 0.04). The citrate group had significantly lower bleeding risk than the systemic heparin group(RR 0.36, 95 % CI 0.21–0.60, P < 0.001) and similar bleeding risk to the regional heparin group(RR 0.34, 95 % CI 0.01–8.24, P = 0.51). The incidences of heparin-induced thrombocytopenia(HIT, RR = 0.46, 95% CI 0.21-1.01, P = 0.05) and hypocalcemia(RR = 4.26, 95% CI 1.69-10.73,P = 0.002) were increased in the heparin and citrate groups, respectively. No significant survival difference was observed between the groups.Conclusions: Given the lower risk of circuit loss, filter failure, bleeding, and HIT, regional citrate should be considered as a better anticoagulation method than heparin for CRRT in critically ill patients without any contraindication to citrate.